LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 2 of total 2

Search options

  1. Article ; Online: G‐quadruplex‐binding small molecules ameliorate C9orf72 FTD/ALS pathology in vitro and in vivo

    Roberto Simone / Rubika Balendra / Thomas G Moens / Elisavet Preza / Katherine M Wilson / Amanda Heslegrave / Nathan S Woodling / Teresa Niccoli / Javier Gilbert‐Jaramillo / Samir Abdelkarim / Emma L Clayton / Mica Clarke / Marie‐Therese Konrad / Andrew J Nicoll / Jamie S Mitchell / Andrea Calvo / Adriano Chio / Henry Houlden / James M Polke /
    Mohamed A Ismail / Chad E Stephens / Tam Vo / Abdelbasset A Farahat / W David Wilson / David W Boykin / Henrik Zetterberg / Linda Partridge / Selina Wray / Gary Parkinson / Stephen Neidle / Rickie Patani / Pietro Fratta / Adrian M Isaacs

    EMBO Molecular Medicine, Vol 10, Iss 1, Pp 22-

    2018  Volume 31

    Abstract: Abstract Intronic GGGGCC repeat expansions in C9orf72 are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively. Repeat ... ...

    Abstract Abstract Intronic GGGGCC repeat expansions in C9orf72 are the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), which are characterised by degeneration of cortical and motor neurons, respectively. Repeat expansions have been proposed to cause disease by both the repeat RNA forming foci that sequester RNA‐binding proteins and through toxic dipeptide repeat proteins generated by repeat‐associated non‐ATG translation. GGGGCC repeat RNA folds into a G‐quadruplex secondary structure, and we investigated whether targeting this structure is a potential therapeutic strategy. We performed a screen that identified three structurally related small molecules that specifically stabilise GGGGCC repeat G‐quadruplex RNA. We investigated their effect in C9orf72 patient iPSC‐derived motor and cortical neurons and show that they significantly reduce RNA foci burden and the levels of dipeptide repeat proteins. Furthermore, they also reduce dipeptide repeat proteins and improve survival in vivo, in GGGGCC repeat‐expressing Drosophila. Therefore, small molecules that target GGGGCC repeat G‐quadruplexes can ameliorate the two key pathologies associated with C9orf72 FTD/ALS. These data provide proof of principle that targeting GGGGCC repeat G‐quadruplexes has therapeutic potential.
    Keywords amyotrophic lateral sclerosis ; C9orf72 ; frontotemporal dementia ; G‐quadruplex ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Subject code 571
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article: C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins

    Mizielinska, Sarah / Adrian M. Isaacs / Andrew J. Nicoll / Anny Devoy / Charlotte E. Ridler / Elizabeth M. C. Fisher / Emma L. Clayton / Frances E. Norona / Ione O. C. Woollacott / Jacqueline Dols / Julian Pietrzyk / Karen Cleverley / Linda Partridge / Melissa Cabecinha / Oliver Hendrich / Pietro Fratta / Sebastian Grönke / Stuart Pickering-Brown / Teresa Niccoli /
    Thomas Moens

    Science. 2014 Sept. 5, v. 345, no. 6201

    2014  

    Abstract: Dipeptide repeat peptides on the attack Certain neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), are associated with expanded dipeptides translated from RNA transcripts of disease-associated genes (see the Perspective by West ... ...

    Abstract Dipeptide repeat peptides on the attack Certain neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), are associated with expanded dipeptides translated from RNA transcripts of disease-associated genes (see the Perspective by West and Gitler). Kwon et al. show that the peptides encoded by the expanded repeats in the C9orf72 gene interfere with the way cells make RNA and kill cells. These effects may account for how this genetic form of ALS causes disease. Working in Drosophila , Mizielinska et al. aimed to distinguish between the effects of repeat-containing RNAs and the dipeptide repeat peptides that they encode. The findings provide evidence that dipeptide repeat proteins can cause toxicity directly. Science , this issue p. 1139 and p. 1192; see also p. 1118
    Keywords amyotrophic lateral sclerosis ; dipeptides ; Drosophila ; genes ; messenger RNA ; proteins ; toxicity ; translation (genetics)
    Language English
    Dates of publication 2014-0905
    Size p. 1192-1194.
    Publishing place American Association for the Advancement of Science
    Document type Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.1256800
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 46/137: Show issues
    + C 27: Show issues
    Z50.00 SC01: Show issues
    Z 8.9: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top